Abstract
Background: A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. Results: Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes. Conclusions: Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.
| Original language | English (US) |
|---|---|
| Article number | 131 |
| Journal | Communications Medicine |
| Volume | 3 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2023 |
Funding
The ADA/EASD Precision Diabetes Medicine Initiative, within which this work was conducted, has received the following support: The Covidence license was funded by Lund University (Sweden) for which technical support was provided by Maria Bj\u00F6rklund and Krister Aronsson (Faculty of Medicine Library, Lund University, Sweden). Administrative support was provided by Lund University (Malm\u00F6, Sweden), University of Chicago (IL, USA), and the American Diabetes Association (Washington D.C., USA). The Novo Nordisk Foundation (Hellerup, Denmark) provided grant support for in-person writing group meetings (PI: L Phillipson, University of Chicago, IL, USA). This study was supported by the National Institute for Health and Care Research Exeter Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. K.G.Y. and J.M.D. are supported by Research England\u2019s Expanding Excellence in England (E3) fund. A.R.K. is supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant KL2TR002490. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. S.R. is funded by a US Department of Veterans Affairs Award IK2-CX001907, and a Webb-Waring Biomedical Research Award from the Boettcher Foundation. J.M.D. is funded by the EFSD Rising Star Fellowship Programme, the UK Medical Research Council (MR/N00633X/1), and a BHF-Turing Cardiovascular Data Science Award (SP/19/6/34809). M.S. is funded by the National Institutes of Health, K01HL157658. The funders had no role in the study design, data extraction or interpretation, writing of the article, or the decision to submit for publication.
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Internal Medicine
- Epidemiology
- Medicine (miscellaneous)
- Assessment and Diagnosis
